Depressive Behavior and Alterations in Receptors for Dopamine and 5-Hydroxytryptamine in the Brain of the Senescence Accelerated Mouse(SAM)-P10

Abstract

The senescence accelerated mouse(SAM)is known as a murine model of aging.SAM consists of senescence accelerated−prone mouse(SAMP)and senescence accelerated−resistant mouse(SAMR).Previous studies reported that SAMP10 exhibits age−related learning impairments and behavioral depression in a tail suspension test after 7 months.We investigated the changes in emotional behavior in a forced swimming test and in receptors for dopamine and 5−hydroxytryptamine(5−HT)in SAMP10.SAMP10 at 8 months showed an increase of immobility in the test compared with SAMR1.Treatment with desipramine(25 mg/kg, i.p., 3 days)in SAMP10 caused a decrease in immobility.In the cortex from SAMP10, [³H]quinpirole binding to D₂/D₃ dopamine receptors increased significantly compared with control SAMR1.In the hippocampus from SAMP10, [³H]8−hydroxy DPAT binding to 5−HT_1A receptor increased.In midbrains from SAMP10, bindings of [³H]quinpirole and [³H]8−hydroxy DPAT increased.[³H]SCH23390 binding to D₁/D₅ receptors and [³H]ketanserin binding to 5−HT₂ receptor in brain regions examined in SAMP10 were similar to those in SAMR1.The present findings represent the first neurochemical evidence of an increase of D₂/D₃ and 5−HT_1A receptors in SAMP10.SAMP10 may be a useful model of aging associated depressive behavior.